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Oral delivery of a functional algal-expressed TGF-β mimic halts colitis in a murine DSS model
Journal of Biotechnology ( IF 4.1 ) Pub Date : 2021-08-12 , DOI: 10.1016/j.jbiotec.2021.08.006
Danielle J Smyth 1 , Bijie Ren 2 , Madeleine P J White 1 , Caitlin McManus 1 , Holly Webster 1 , Vivien Shek 1 , Caroline Evans 3 , Jagroop Pandhal 3 , Francis Fields 2 , Rick M Maizels 1 , Stephen Mayfield 2
Affiliation  

Inflammatory bowel disease (IBD) is a set of immunological disorders which can generate chronic pain and fatigue associated with the inflammatory symptoms. The treatment of IBD remains a significant hurdle with current therapies being only partially effective or having significant side effects, suggesting that new therapies that elicit different modes of action and delivery strategies are required. TGM1 is a TGF-β mimic that was discovered from the intestinal helminth parasite Heligmosomoides polygyrus and is thought to be produced by the parasite to suppress the intestinal inflammation response to help evade host immunity, making it an ideal candidate to be developed as a novel anti-inflammatory bio-therapeutic. Here we utilized the expression system of the edible green algae Chlamydomonas reinhardtii in order to recombinantly produce active TGM1 in a form that could be ingested. C. reinhardtii robustly expressed TGM1, and the resultant recombinant protein is biologically active as measured by regulatory T cell induction. When delivered orally to mice, the algal expressed TGM1 is able to ameliorate weight loss, lymphadenopathy, and disease symptoms in a mouse model of DSS-induced colitis, demonstrating the potential of this biologic as a novel treatment of IBD.



中文翻译:

口服功能性藻类表达的 TGF-β 模拟物可阻止小鼠 DSS 模型中的结肠炎

炎症性肠病(IBD)是一组免疫性疾病,可产生与炎症症状相关的慢性疼痛和疲劳。IBD 的治疗仍然是一个重大障碍,目前的疗法仅部分有效或具有显着的副作用,这表明需要引发不同作用模式和递送策略的新疗法。TGM1 是一种 TGF-β 模拟物,是从肠道蠕虫寄生虫Heligmosomoides polygyrus中发现的,被认为是由寄生虫产生的,可抑制肠道炎症反应,帮助逃避宿主免疫,使其成为开发新型抗肿瘤药物的理想候选者。 -炎症生物治疗。在这里,我们利用可食用绿藻莱茵衣藻的表达系统来重组生产可摄入形式的活性 TGM1。莱茵衣藻强烈表达 TGM1,并且通过调节性 T 细胞诱导测量,所得重组蛋白具有生物活性。当口服给小鼠时,藻类表达的 TGM1 能够改善 DSS 诱导的结肠炎小鼠模型的体重减轻、淋巴结肿大和疾病症状,这证明了这种生物制剂作为 IBD 新型治疗方法的潜力。

更新日期:2021-08-23
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